Based on our experience with the transplantation of islets into syngeneic diabetic rats, we consider this a highly feasible experimental approach for the normalization of blood sugars. We have demonstrated that (1) islets can be viably maintained in tissue culture for periods up to 55 days (2) the cultured islets can be used as transplantation material in rats with hyperglycemia of short and long-term duration and (3) islets lodged in the liver do not adversely affect hepatic metabolism. One of the major obstacles to successful transplantation in the human is the immune barrier which leads to rapid rejection of transplanted pancreatic islets. We wish to extend our studies and develop expertise in methods whereby islets can be transplanted across histocompatibility barriers in the rat. Two approaches will be followed namely (1) an induction of changes in cell surface components in islets by a variety of culturing techniques and (2) by manipulation of the recipient's immune responsiveness by the stimulation of enhancing antibodies or by the induction of specific tolerance to donor tissues in the host.